Self-assembly, cytocompatibility, and interactions of desmopressin with sodium polystyrene sulfonate

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Caliari, Ana B. ; Bicev, Renata N. ; da Silva, Caroline C. ; de Souza, Sinval E. G. ; da Silva, Marta G. ; Souza, Louise E. A. ; de Mello, Lucas R. ; Hamley, Ian W. ; Motta, Guacyara ; Degrouard, Jeril ; Tresset, Guillaume ; Quaresma, Alexandre J. C. ; Nakaie, Clovis R. ; da Silva, Emerson R.

• Document type: Journal article
• Source: SOFT MATTER; v. N/A, p. 17-pg., 2024-11-19.

Abstract

Peptide-polymer systems hold strong potential for applications in nanotherapeutics. Desmopressin, a synthetic analogue of the antidiuretic hormone arginine vasopressin, may serve as a valuable case of study in this context since it is a first-line treatment for disorders affecting water homeostasis, including diabetes insipidus. It also has an established use as a hemostatic agent in von Willebrand disease, and recently, its repurposing has been suggested as a neoadjuvant in the treatment of certain types of cancer. Despite its well-documented clinical uses, studies on the supramolecular organization of desmopressin and its association with polymers remain scarce, limiting the therapeutic benefits of these nanostructured arrays. Here, we investigate the self-assembly of desmopressin and its association with sodium polystyrene sulphonate (NaPSS), a potassium-binding polymer used to treat hyperkalemia. Using structural techniques such as small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and atomic force microscopy combined with infrared nanospectroscopy (AFM-IR), we identified that desmopressin associates with NaPSS to form hybrid fibrillar nanoassemblies characterized by beta-turn enriched domains and the appearance of beta-sheet content. In vitro cytotoxicity assays conducted on breast cancer cell lines MCF-7 and MDA-MB-231 showed that NaPSS/desmopressin complexes are well-tolerated by the non-metastatic MCF-7 cells while displaying inhibitory effects against the metastatic MDA-MB-231 cells. The findings presented here, which demonstrate the successful association between two clinically validated drugs and the ability of the hybrid matrix to modulate cell interactions, potentially contribute to the design of peptide-polymer therapeutic systems. (AU)

• FAPESP's process: 21/04885-3 - Synthesis and structural investigation of peptides and polymers: from innovation in the synthesis method to the study of some physiological relevant peptides
• Grantee: clovis ryuichi nakaie
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03056-6 - Ultrastructural characterization of bioactive nanoscaffolds
• Grantee: Emerson Rodrigo da Silva
• Support Opportunities: Research Grants - Initial Project
• FAPESP's process: 23/18385-8 - Bioinspired Coacervates Based on Bioactive Peptides Derived from Viral Proteomes
• Grantee: Emerson Rodrigo da Silva
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 17/22047-0 - Integrins and the Urokinase Plasminogen Activator Receptor (uPAR) interaction: participation of Plasma Kallikrein-Kinin System and Proteoglycans.
• Grantee: Guacyara da Motta
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/19719-1 - Bioactive peptide matrices: from molecular structure to biomedical applications
• Grantee: Lucas Rodrigues de Mello
• Support Opportunities: Scholarships in Brazil - Doctorate